The broad purpose of this proposal is to utilize the unique capabilities of a large environmental chamber to achieve a better understanding of the mechanisms underlying the renal response to chronic hypercapnia and hypocapnia. The chamber permits carbon dioxide tension to be fixed in vivo at any desired level between 15 and 150 mmHg. Specific objectives include: I. Examination of the role of pH as a mediator of the renal response to chronic alterations in PaCO2. 1. The role of systemic pH in the renal response to sustained hypercapnia. 2. The effect of chronic hypocapnia on acid-base balance during chronic metabolic alkalosis. 3. The effect of chronic HC1-acidosis on the renal adaptation to persistent hypercapnia. II. Influence of chronic alterations in PaCO2 on tubular transport systems. 1. Micropuncture study of proximal and distal tubular responses to chronic alterations in PaCO2. 2. "Stop-flow" examination of the renal response to chronic alterations in PaCO2. 3. The renal response to diuretics during chronic hypercapnia and chronic hypocapnia. III. Use of the chamber to probe te renal response to metabolic acid-base disturbances. 1. The influence of secondary hypocapnia on plasma bicarbonate in chronic metaboli alkalosis. 2. The effect of chronic hypercapnia on the renal response to mineral acid loads. 3. The role of secondary hypocapnia in chronic H2SO4 acidosis. IV. Use of the chamber to probe other renal regulatory systems. The effect of chronic PaCO2 levels on the renal regulation of sodium balance. V. Response of the diseased kidney to chronic alterations in PaCO2.